Pharmaceutical Substances Syntheses, Patents, Applications - Part 3 doc

Acetylcholine chloride A 2 1 hydroxide RN: 56-13-3 MF: C,H,,NO, MW: 163.22 bromide RN: 66-23-9 MF: C,H,,BrNO, MW: 226.1 1 EINECS: 200-622-4 LD,,,: 170 mglkg (M, s.c.) trimethyl- 2-chloro- choline Acetylcholine chloride arnine (I) ethanol (11) chloride (In) OH- HCI N I + 8 + H~C\+fi~~ 4 111 + H,c/~\ CH3 ethylene choline oxide hydroxide I + + ( Acetylcholine chloride I Reference(s); Baeyer, A. v.: Justus Liebigs Ann. Chem. (JLACBF) 142, 235 (1867). Nothnagel: Arch. Pharm. (Weinheim, Ger.) (ARPMAS) 232,265 (1894). Fourneau, E.; Page, H.J.: Bull. Soc. Chim. Fr. (BSCFAS) [4] 15,544 (1914). DE 801 210 (BASF; appl. 1948). US 1 957 443 (Merck & Co.; 1934; appl. 1931). US 2 012 268 (Merck & Co.; 1935; appl. 1931). US 2 013 536 (Merck & Co.; 1935; appl. 1931). Formulation(s): amp. 20 mg; eye drops 1 % Trade Name(s): D: Miochol-E (CIBA Vision) J: Acetylcholine (Roche) I: Farmigea acetilcolina Neucholin-A (Zeria); wfm (Farmigea); wfm Ovisot (Daiichi); wfm 22 A Acetylcysteine Acet ylcysteine ATC: RO5CBOl; SOlXA08; V03AB23 Use: mucolytic agent RN: 616-91-1 MF: C5H9N03S MW: 163.20 EINECS: 210-498-3 LD,,,: 400 mglkg (M, i.p.); 3800 mglkg (M, i.v.); 7888 mglkg (M, p.0.): 1 140 mglkg (R, i.v.); 5050 mglkg (R, p.0.); 700 mglkg (dog, i.p.1; 700 mg/kg (dog, i.v.); >1 g/kg (dog, p.0.) CN: N-acctyl-L-cysteine monosodium salt RN: 19542-74-6 MF: C,H,NNaO,S MW: 185.18 EINECS: 243-143-6 LD,,,: 3800 mglkg (M, i.v.); 2559 mglkg (R,i.v.) monoammonium salt RN: 50807-78-8 MF: C,H,NO,S . H,N MW: 180.23 HCI 0 0 CH3COONo Y2 0 H,O + HS4~~~~ H,C~O~CH, L-cysteine acetic anhydride hydrochloride monohydrate Acdylcysteine I Keference(s): US 3 091 569 (Mead Johnson;. 28.5.1963; appl. 26.8.1960). US 3 184 505 (Mead Johnson; 18.5.1965; ap$. 18.6.1962). Smith, H.A.; Gorin, G.: J. Org. Chem. (JOCEAH) 26,820 (1961). ammonium sulf (mucolysis of bronchial mucus by nebulization): DOS 2 305 271 (Bristol-Myers; appl. 2.2.1973; USA-prior. 3.2.1972). Formulation(s): amp. 300 mg (as monosodium salt); cps. 200 mg; eff. tabl. 100 mg, 200 mg, 600 mg; f. c. tabl. 100 mg, 200 mg, 600 mg; gran. 10 mg, 100 mg. 200 mg, 600 mg; lyo. for syrup I00 mg; syrup 200 mg1lO ml; tabl. I00 mg, 200 mg, 600 mg Trade Name(s): D: ACC (Hexal) Acemuc (betapharm) Fluimucil-1001-200 (Zambon) Rinofluimucil (1npharzam)- comb. numerous combination and generic preparations F: Broncoclar (Oberlin) Codotussyl (Whitchall) Euronac (Europhta) Exomuc (Bouchara) Fluimucil (Zambon) Fluimucil Antibiotic 750 (Zambon) Gcnac (GCnCvrier) Mucolator (Abbott) Mucomyst (Bristol-Myers Squibb) Mucothiol (SCAT) Rhinofluimucil (D6bat)- comb. Solmucol (GCnCvrier) Tixair (Byk) GB: Iluhe (Alcon)-comb. Parvolex (Evans) I: Brunac (Bruschettini) Fluimucil (Zambon) Mucisol (Deca) Rinofluimucil (Zambon). comb. J: Acetein (Senju) Mucofilin Sol. (Eisai) USA: Mucosit (Dey) Acetyldigitoxin A 23 Acety ldigitoxin ATC: C01AAOl Use: cardiotonic, cardiac glycoside RN: 11 11 -39-3 MF: C43HM0,4 MW: 806.99 EINECS: 214-178-4 LD,,,: >30 mg/kg (g. p., p.0.); 514 pdkg (cat, i.v.); 250 pglkg (cat, p.0.) CN: (3~,5~)-3-[(0-3-O-acetyl-2,6-dideoxy-~-~-ribo-hexopyranosy-(1+4)-0-2,6-dideoxy-~-~-ribo- hexopyranosyl-(1 -14)-2,6-dideoxy-P-D-ribo-hexopyranosyl)oxy]- 14-hydroxycard-20(22)-enolide H enzymatic hydrolysis digilanidase b . 1 I - OH OH lonatoside A 0-acetyldigitoxin (I) Acetyldigitoxin u 0 CH, K Acetyldigitoxin 0 H3C- 0 rC~3 THF. TosOH H,C+O O-CH, digitoxin triethyl orthoocetote a Stoll, A. et a].: Helv. Chim. Acta (HCACAV) 34,397 (1951). Gisvold, 0.: J. Pharm. Sci. (JPMSAE) 61, 1320 (1972). HU 155 716 (Richter Gedeon; appl. 20.1.1968). DE 925 047 (Sandoz; appl. 1954; CH-prior. 1952). b DE 2 01 0 422 (Boehringer Ing.; appl. 5.3.1970). alternative synthesis: DE 2 206 737 (Boehringer Mannh.; appl. 12.2.1972) (a-Acetyldigoxin, q. v.). Formulation(s): tabl. 0.2 mg Trade Name(s): D: Acylanid (Sandoz); wfm F: Acylanid (Sandoz); wfm USA: Acylanid (Sandoz); wfm ATC: C01AA02 Use: cardiotonic, cardiac glycoside RN: 551 1-98-8 MF: C4311hh015 MW: 822.99 EINECS: 226-855-1 LD,,,: 3300 vg/kg(g. p., p.0.); 200 vg/kg (cat, p.0.) CN: (3~,5~,12~)-3-[(0-3-0-acetyl-2,6-dideoxy-~-~-ribo-hexopyranosy-(+4)-0-2,6-dideoxy-~-~-ribo- hexopyranosyl-(I +4)-2,6-dideoxy-P-D-ribo-hexopyranosyl)oxy]- 12,14-dihydroxycard-20(22)-enolide enzymatic hydrolysis digilanidose ocetyldigitoxin partition of the methonol + solution between digilonide enzymatic hydrolysis , - acetyldigoxin Hz0 Ond CHC13 + (lonotoside A. B. C) acetylgitoxin 1. (CH30),S0,. CH,CON(CH,), 2. HCOOH 1. dimethyl sulfate 2. formic acid OH digoxin sodium acetate Reference(s): a Fieser, L.F.; Fieser, M.: Steroide, p. 801, Verlag Chemie, Weinheim 1961. b GB 1 162 614 (Heilmittelwerke Wien; appl. 1.2.1968; A-prior. 7.2.1967). Gisvold, 0.: J. Pharm. Sci. (JPMSAE) 61, 1320 (1972). alternative syntheses: DE 2 010 422 (Boehringer Ing.; appl. 5.3.1970). (Acetyldigitoxin, q. v.). Rietbrock, N.; Kuhlmann, J.: Naunyn-Schmiedeberg's Arch. Pharmacol. (NSAPCC) 279,413 (1973). Formulation(s): sol. 0.5 mglml; tabl. 0.25 mg, 0.2 mg Trade Name(s): D: Card-Hydergin (Sandoz)- Lanadigin (Promonta); Nitro-Sandolanid (Sandoz)- comb.; wfm wfm comb.; wfm Digi-Complamin Lanadigin EL (Promonta); Sandolanid (Sandoz) (Beecham-Wii1fing)-comb.; wfm F: Acygoxine (Sandoz); wfm wfm Lanadigin + Theophyllin I: Cedigossina (Sandoz) (Promonta)-comb.; wfm ATC: COIAA02 Use: cardiotonic, cardiac glycoside RN: 5355-48-6 MF: C,,H,O1, MW: 822.99 EINECS: 226-337-5 LD,,: 2400 kg/kg (g, p., p.0.); 422 !%kg (dog, p.o.1 CN: (3~,5~,12~)-3-[(0-4-0-acetyl-2,6-dideoxy-[oxy-~-~-ribo- hexopyranosyl-(l~4)-2,6-dideoxy-~-~-ribo-hexopyranosyl)oxy]- 12,14-dihydroxycard-20(22)-enolide isolation and extroction from the leaves of Digitalis lanota dicyclohexyl- carbodiimide a Hopponen, R.E.; Gisvold, 0.: J. Am. Pharm. Assoc. (JPHAA3) 41, 146 (1952). Rangaswami, S. et al.: Indian J. Pharm. (IJPAAO) 17,253 (1955). b HU 7 147 (Richter Gedeon; appl. 5.6.1972). alternative syntheses: Haberland, G.: Arzneim Forsch. (ARZNAD) 15,481 (1965). Graf, E.; Pfaff, J.: Arch. Pharm. (Weinheim, Ger.) (ARPMAS) 307,943 (1974). DOS 2 826 532 (LEK tovarna farm.; appl. 16.6.1978; YU-prior. 22.6.1977). medical use: DOS 1 921 307 (Boehringer Ing.; appl. 25.4.1969) addition to DOS 1 767 553. Formulation(s): tabl. 0.1 mg, 0.2 mg Trade Name(s): D: Beta-Acetyldigoxin Beta- Acetyldigoxin- Digotab (ASTA Medica (ratiopharm) ratiopharm 0,l mg/0,2 mg AWD) Beta-Acetyldigoxin R.A.N. (ratiopharm) Digox (ct-Arzneimittel) = glycotop (R.A.N.) Digostada 0.21-mite Digoxin-Didier (S tadapharm) (Hormosan) Digostade (Stada) Gladixol (Corax) 28 A Acetylsalicylic acid Kardiamed (Medice) numerous combination Cardioreg (Nattermann); Novodigal (Beiersdorf) preparations wfm Stillacor (Wolff) I: Beta-Acigoxia (Inverni della Beffa); wfm Acetylsalicylic acid (Acidum acetylsalicylicum; Aspirin) ATC: AOlADO5; B01 ACO6; M01BA03; N02BA01; N02BA5 1 Use: analgesic, antipyretic, antirheumatic, platelet aggregation inhibitor RN: 50-78-2 MF: CyH,04 MW: 180.16 EINECS: 200-064-1 LD,,: 280 mglkg (M, i.p.); 250 mgkg (M, p.0.); 1520 mgkg (M, s.c.); 340 mglkg (R, i.p.); 200 mgkg (R, p.0.); 1600 mglkg (R, s.c.); 1075 mgkg (g. p., p.0.); 1010 mgkg (rabbit, p.0.); 681 mglkg (dog, i.v.); 700 mglkg (dog, p.0.) CN: 2-(acety1oxy)benzoic acid aluminum salt RN: 147-31-9 MF: C27H2,A10,2 MW: 564.44 calcium salt RN: 69-46-5 MF: Cl,H14Ca0, MW: 398.38 EINECS: 200-707-6 lithium salt RN: 552-98-7 MF: CyH7Li04 MW: 186.09 EINECS: 209-029-5 sodium salt RN: 493-53-8 MF: CyH7Na04 MW: 202.14 EINECS: 207-777-7 LD,,: 730 mglkg (M, i.p.); 1450 mgkg (R, i.p.) magnesium salt RN: 132-49-0 MF: C18H14Mg0, MW: 382.61 EINECS: 205-062-4 LD,,: 620 mglkg (M, s.c.) lysine salt (1:l) RN: 62952-06-1 MF: CyH,04. C,H,4N202 MW: 326.35 LD,,: 950 mgkg (M, i.v.); 3270 mgkg (M, p.0.); 1525 mgkg (R, i.v.); 4350 mgkg (R, p.0.) salicylic acetic anhydride 1 Acetylsalicylic acid acid Reference(s): Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 13,90. US 3 235 583 (Norwich Pharmacal; 15.2.1966; appl. 22.7.1964). acetylation in presence of pyridine for avoidance of formation of acetylsalicylic anhydride and acetylsalicylsalicylic acid: DOS 2 635 540 (A. L. de Week, H. Bundgaard; appl. 6.8.1976). acetylation in presence of H,SO,: US 2 731 492 (J. Kamlet; 1956; appl. 1954). crystallization: US 2 890 240 (Monsanto; 1959; appl. 1957). Acetylsulfafurazole A 29 aluminum salts: DRP 585 986 (Chinoin; appl. 1931 ; H prior. 193 I). US 2 698 332 (Reheis Comp.; 1954; appl. 1951). US 2 918 485 (Keystone Chemurgic Corp.; 1959; appl. 1955). GB 888 666 (Hardman & Holden; appl. 1959). aluminum acetylsalicylate glutaminate: DOS 2 909 829 (Kyowa Hakko; appl. 13.3.1979; J-prior. 13.3.1978). Formulation(s): cps. 325 mg, 500 mg, suppos. 125 mg, 150 mg, 300 mg; tabl. 50 mg, 75 mg. 100 mg, 300 mg, Trade Name(s): D: Alka-Seltzer (Bayer) Aspirin (Bayer; 1899) Aspisol (Bayer; as DL- lysine salt) Aspro (Roche Nicholas) ASS Dura (durachemie) ASS-ratiopharm (ratiopharm) Godamed (Pfleger) Micristin (OPW) Miniasal (OPW) Romigal (Romogal-Werk) Santasal (Merckle) Toga1 (Togal) GB : numerous combination preparations F: Actron (Bayer)-comb. Afebry (Ga1ephar)-comb. Alka-Seltzer (Bayer)-comb. Antigrippine (SmithKline Beecham)-comb. AspCgic 500 (SynthClabo; as lysine salt) Aspirine BayCr (Bayer) I: Aspirine duRh6ne (Bayer) - Aspirine pH 8 (3M SantC) Aspirine Upsa (UPSA) Aspirine Upsa Vitamine C (UPSA)-comb. Aspirine Vitamine C (0berlin)-comb. Aspirisucre (Arkomedika) Aspro (Nicholas) Catalgine (Schwarz) Claragine (Nicholas) KardCgic (SynthClabd) Rhonal (Thtraplix) SargCpirine (ASTA Mtdica) Solupsan (UPSA) numerous combination preparations Angettes (Bristol-Myers) Aspan (Hoechst)-comb. Aspirin (Bayer) Caprin (Sinclair) Disprin CO (Reckitt & Colman) Nu-Seals Aspirin (Lilly) Post MI (Ashbourne) numerous combination preparations Ac Acsal (Formulario Naz.; Tariff. Nazionale; Scfm; Iema; Farmacologico Milanese) Acesal (Geymonat) Alupir (Farmacologico Milanese; as aluminum salt) Aspergum (Farmades) Aspirina (Bayer) Aspirinetta (Bayer) Aspro (Roche) Bufferin (Bristol-Myers Squibb) Cemirit (Bayer) Endydol (Guidotti) Kilios (Carlo Erba) numerous combination preparations J: generic preparations USA: Acuprin (Richwood) Ecotrin (SmithKline Beecham Consumer) Equagesic (Wyeth-Ayerst) Fiorinal (Novartis) Halfprin (Kramer) Norgeric (3M) Percotan (Endo) Roboxisal (Robins) Acetylsulfafurazole ATC: SO~AB (Acetylsulfisoxazole; Sulfisoxazole Acetyl) Use: antibacterial RN: 80-74-0 MF: C,,H,,N,O,S MW: 309.35 EINECS: 201-305-3 I CN: N-[(4-aminophenyl)sulfonyl]-N-(3,4-dimethyl-5-isoxazolyl)acetamide 30 A Acexamic acid sulfafurazole acetic anhydride (4. v.) H 1. acetone. pyridine. 40 OC CH~ 2.3 Z oq. NH,, 0 "C 0 0 H2N Reference(s): US 2 721 200 (Roche; 1955; appl. 1953). HC 0 y H2N Formulation(s): susp. 500 mg/5 ml Trade Name(s): USA: Eryzole (Alra) Acetylsulfofurozole Pediazole (Ross) Acexamic acid (Acide acexamique) ATC: D03A Use: antifibrinolytic RN: 57-08-9 MF: C8H,,N03 MW: 173.21 EINECS: 200-310-8 CN: 6-(acety1amino)hexanoic acid sodium salt RN: 7234-48-2 MF: C,H,,NNaO, MW: 195.19 EINECS: 230-635-0 N-acetyl-c- coprolactarn arninocaproic acid (1) Reference(s): Offe, H.A.: Z. Naturforsch., B: Anorg. Chem., Org. Chem., Biochem., Biophys., Biol. (ZENBAX) 2, 182 (1947). FR-M 2 332 (Rowa; appl. 1963). Acexamic acid Formulation(s): amp. 5 g (as sodium salt); cps. 300 mg (as zinc salt); ointment 5 % (as sodium salt); susp. 300 mg (as zinc salt) (q v.) Trade Name(s): F: PlastCnan (Isopharm) PlastCnan NComycine I: Plastenan (Italfarmaco); (1sopharm)-comb. wfm . p.0.) CN: (3~ ,5~ ) -3 -[ ( 0 -3 -O-acetyl-2,6-dideoxy- ~-~ -ribo-hexopyranosy-(1+4 )-0 -2 ,6-dideoxy- ~-~ -ribo- hexopyranosyl-(1 -1 4 )-2 ,6-dideoxy-P-D-ribo-hexopyranosyl)oxy ]- 14-hydroxycard-20(22)-enolide. 551 1-9 8-8 MF: C 431 1hh015 MW: 822.99 EINECS: 22 6-8 5 5-1 LD,,,: 33 00 vg/kg(g. p., p.0.); 200 vg/kg (cat, p.0.) CN: (3~ ,5~,12~ ) -3 -[ ( 0 -3 -0 -acetyl-2,6-dideoxy- ~-~ -ribo-hexopyranosy-(+4 )-0 -2 ,6-dideoxy- ~-~ -ribo-. (dog, p.o.1 CN: (3~ ,5~,12~ ) -3 -[ ( 0-4 -0 -acetyl-2,6-dideoxy-[oxy- ~-~ -ribo- hexopyranosyl-(l~4 )-2 ,6-dideoxy- ~-~ -ribo-hexopyranosyl)oxy ]- 12,14-dihydroxycard-20(22)-enolide isolation and extroction